Abstract
The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Antigens, Polyomavirus Transforming / physiology*
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Base Sequence
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CDC2-CDC28 Kinases*
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Transformation, Viral
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases / metabolism
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DNA Primers
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DNA-Binding Proteins / metabolism
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E2F Transcription Factors
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G1 Phase
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Mice
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Molecular Sequence Data
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Phosphoproteins*
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / metabolism
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Proteins / metabolism*
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Retinoblastoma-Binding Protein 1
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Retinoblastoma-Like Protein p130
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S Phase
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Transcription Factor DP1
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Transcription Factors / metabolism*
Substances
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Antigens, Polyomavirus Transforming
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Arid4a protein, mouse
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Carrier Proteins
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Cell Cycle Proteins
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DNA Primers
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DNA-Binding Proteins
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E2F Transcription Factors
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Phosphoproteins
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Proteins
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Rbl2 protein, mouse
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Retinoblastoma-Binding Protein 1
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Retinoblastoma-Like Protein p130
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Transcription Factor DP1
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Transcription Factors
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Protein Serine-Threonine Kinases
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CDC2-CDC28 Kinases
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Cdk2 protein, mouse
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Cyclin-Dependent Kinase 2
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Cyclin-Dependent Kinases